0000000000450408
AUTHOR
Niels Schaft
Strong and sustained effector function of memory- versus naïve-derived T cells upon T-cell receptor RNA transfer: Implications for cellular therapy
Current protocols used to select CMV-specific T cells for adoptive immunotherapy focus on virus-specific memory T cells from seropositive donors. However, this strategy is not feasible in patients undergoing allogeneic haematopoietic stem-cell transplantation (HSCT) from CMV-seronegative donors. Here, we redirected T cells of CMV-seronegative donors with a human genetically engineered TCR recognizing an HLA-A*0201-binding peptide epitope of CMVpp65. To facilitate clinical translation of this approach, we used a non-viral expression system based on in vitro transcribed RNA and electroporation. Although memory and naive-derived T-cell subsets were both efficiently transfected by TCR-RNA, memo…
Editorial: CAR T-cells: novel therapeutic approaches in the new era of cancer immunotherapy
Immunotherapy has emerged as one of the most effective treatments capable of overcoming tumor resistance mechanisms due to its ability to modulate the patient’s immune response against cancer. Personalized anti-tumor therapy based on T cells engineered to express a cancer-specific chimeric antigen receptor (CAR) acts directly on the immune system of patients. Specifically, this therapy enhances the recognition of cancer cells by T lymphocytes, thus promoting their elimination. In this Research Topic several aspects of CAR T-cell therapy, with particular emphasis on novel findings aimed at ameliorating the effectiveness of CAR T-cell-based immunotherapy and reducing side effects, are describ…
Generation of CD8+T cells expressing two additional T-cell receptors (TETARs) for personalised melanoma therapy
Adoptive T-cell therapy of cancer often fails due to the tumor cells' immune escape mechanisms, like antigen loss or down-regulation. To anticipate immune escape by loss of a single antigen, it would be advantageous to equip T cells with multiple specificities. To study the possible interference of 2 T-cell receptors (TCRs) in one cell, and to examine how to counteract competing effects, we generated TETARs, CD8(+) T cells expressing two additional T-cell receptors by simultaneous transient transfection with 2 TCRs using RNA electroporation. The TETARs were equipped with one TCR specific for the common melanoma antigen gp100 and one TCR recognizing a patient-specific, individual mutation of…